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INDEX
• OVERVIEW
• INTRODUCTION
• PROBLEM
• PROTEIN-BASED MEMORY
• WHY BACTERIORHODOPSIN?
• STRUCTURE OF BACTERIORHODOPSIN
• DATA ERASING
• DATA REFRESHING
• MERITS
• CONCLUSION
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PROTEIN MEMORY
OVERVIEW
While magnetic storage devices have been in use since the middle 1950's, today's
computers and volumes of information require increasingly more efficient and faster
methods of storing data. While the speed of integrated circuit has increased steadily over
the past ten to fifteen years, the limits of these systems are rapidly approaching. In
response to the rapidly changing face of computing and demand for physically smaller,
greater capacity, a number of alternative methods to integrated circuit information storage
have surfaced recently. Protein-based optical memory storage using protein
bacteriorhodopsin is a promising one amongst them. Bacteriorhodopsin is a light-
harvesting protein from bacteria that live in salt marshes that has shown some promise as
feasible optical data storage.
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PROTEIN MEMORY
Introduction
Since the dawn of time, man has tried to record important events and techniques
for everyday life. At first, it was sufficient to paint on the family cave wall how one
hunted. Then came people who invented spoken languages and the need arose to record
what one was saying without hearing it firsthand. Therefore, years later, earlier scholars
invented writing to convey what was being said. Pictures gave way to letters which
represented spoken sounds. Eventually clay tablets gave way to parchment, which gave
way to paper. Paper was, and still is, the main way people convey information.
However, in the mid twentieth century computers began to come into general use.
Computers have gone through their own evolution in storage media. In the forties, fifties,
and sixties, everyone who took a computer course used punched cards to give the
computer information and store data. In 1956, researchers at IBM developed the first disk
storage system. This was called RAMAC (Random Access Method of Accounting and
Control).
Since the days of punch cards, computer manufacturers have strived to squeeze
more data into smaller spaces. That mission has produced both competing and
complementary data storage technology including electronic circuits, magnetic media like
hard disks and tape, and optical media such as compact disks.
Magnetic storage technologies used for most computer hard disks are the most
common and provide the best value for fast access to a large storage space. At the low
end, disk drives cost as little as 25 cents per and provide access time to data in ten
milliseconds. Drives can be ganged to improve reliability or throughput in a Redundant
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Array of Inexpensive Disks (RAID). Magnetic tape is somewhat slower than disk, but it is
significantly cheaper per megabyte. At the high end, manufacturers are starting to ship
tapes that hold 40 gigabytes of data. These can be arrayed together into a Redundant
Array of Inexpensive Tapes (RAIT), if the throughput needs to be increased beyond the
capability of one drive. For randomly accessible removable storage; manufacturers are
beginning to ship low-cost cartridges that combine the speed and random access of a hard
drive with the low cost of tape. These drives can store from 100 megabytes to more than
one gigabyte per cartridge.
Standard compact disks are also gaining a reputation as an incredibly cheap way
of delivering data to desktops. They are the cheapest distribution medium around when
purchased in large quantities ($1 per 650 megabyte disk). This explains why so much
software is sold on CD-ROM today. With desktop CD-ROM recorders, individuals are
able to publish their own CD-ROMs.
With existing methods fast approaching their limits, it is no wonder that a number
of new storage technologies are developing. Currently, researches are looking at protein-
based memory to compete with the speed of electronic memory, the reliability of
magnetic hard-disks, and the capacities of optical/magnetic storage. We contend that
three-dimensional optical memory devices made from bacteriorhodopsin utilizing the two
photon read and write-method is such a technology with which the future of memory lies.
Problem
The demands made upon computers and computing devices are increasing each
year, speeds are increasing at an extremely fast clip. However, the RAM used in most
computers is the same type of memory used several years ago. The limits of making RAM
denser are being reached. Surprisingly, these limits may be economical rather than
physical. A decrease by a factor of two in size will increase the cost of manufacturing of
semiconductor pieces by a factor of 5.
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generally 70ns; however 60ns and 100ns modules are available. The lower the
nanosecond rating, the more the module will cost. Currently, a 64MB DIMM costs over
$400. All DIMMs are 12cm by 3cm by 1cm or about 36 cubic centimeters. Whereas a 5
cubic centimeter block of bacteriorhodopsin studded polymer could theoretically store
512 gigabytes of information. When this comparison is made, the advantage becomes
quite clear. Also, these bacteriorhodopsin modules could also theoretically run 1000 times
faster.
In response to the demand for faster, more compact, and more affordable memory
storage devices, several alternatives have appeared in recent years. Among the most
promising approaches include memory storage using protein-based memory.
Protein-Based Memory
There have been many methods and proteins researched for use in computer
applications in recent years. However, among the most promising approaches, the main
one is 3-Dimensional Optical RAM storage using the light sensitive protein
bacteriorhodopsin.
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PROTEIN MEMORY
For years these researchers worked in secret, mainly at their blackboards, plotting
and planning. Now they are beginning to conduct small forays in the laboratory, and their
few successes to date lead them to believe they were on the right track. "We have a long
way to go before carbon-based electronics replace silicon-based electronics, but we can
see now that we hope to revolutionize computer design and performance," said Robert R.
Birge, a professor of chemistry, Carnegie-Mellon University, Pittsburgh. "Now it's only a
matter of time, hard work, and some luck before molecular electronics start having a
noticeable impact." Molecular electronics is so named because it uses molecules to act as
the "wires" and "switches" of computer chips. Wires may someday be replaced by
polymers that conduct electricity, such as polyacetylene and polyphenylenesulphide.
Another candidate might be organometallic compounds such as porphyrins and
pthalocyanines which also conduct electricity. When crystallized, these flat molecules
stack like pancakes, and metal ions in their centers line up with one another to form a one-
dimensional wire.
Many organic molecules can exist in two distinct stable states that differ in some
measurable property and are interconvertable. These could be switches of molecular
electronics. For example, bacteriorhodopsin, a bacterial pigment, exists in two optical
states: one state absorbs green light, the other orange. Shinning green light on the green-
absorbing state converts it into the orange state and vice versa. Birge and his coworkers
have developed high density memory drives using bacteriorhodopsin. Although the idea
of using organic molecules may seem far-fetched, it happens every day throughout nature.
"Electron transport in photosynthesis one of the most important energy generating
systems in nature, is a real-world example of what we're trying to do," said Phil Seiden,
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manager of molecular science, IBM, Yorkstown Heights, N.Y. Birge, who heads the
Center for Molecular Electronics at Carnegie-Mellon, said two factors are driving this
developing revolution, more speed and less space.
Chip designers have been cramming more transistors into less space since Jack
Kilby at Texas Instruments and Robert Noyce at Fairchild Semiconductor first showed
how to put multitudes on electronic components on a slab of silicon. But 16 megabytes
may be near the end of the road. As bits get smaller and loser together, "crosstalk"
between them tends to degrade their performance. If the components were pushed any
closer they would short circuit. Physical limits have triumphed over engineering. That is
when chemistry will have its day. Carbon, the element common to all forms of life, will
become the element of computers too. "That is when we see electronics based on
inorganic semiconductors, namely silicon and gallium arsenide, giving way to electronics
based on organic compounds," said Scott E. Rickert, associate professor of
macromolecular science, Case Western Reserve University, Cleveland, and head of the
school's Polymer Micro device Laboratory. "As a result," added Rickert, "we could see
memory chips store billions of bytes of information and computers that are thousands
times faster. The science of molecular electronics could revolutionize computer design."
But even if it does not, the research will surely have a major impact on organic chemistry.
"Molecular electronics presents very challenging intellectual problems on organic
chemistry, and when people work on challenging problems they often come up with
remarkable, interesting solutions," said Jonathan S. Lindsey, assistant professor of
chemistry, Carnegie-Mellon University. "Even if the whole field falls through, we'll still
have learned a remarkable amount more about organic compounds and their physical
interactions than we know now. That's why I don't have any qualms about pursuing this
research." Moreover, many believe that industries will benefit regardless of whether an
organic-based computer chip is ever built. For example, Lindsey is developing an
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automated system, as well as the chemistry to go along with it, for synthesizing complex
organic compounds analogous to the systems now available for peptide and nucleotide
synthesis. And Rickert is using technology he developed foe molecular electronic
applications to make gas sensors that are both a thousand times faster and more sensitive
than conventional sensors.
For now, the molecular electronics revolution is in the formative stage, and most
of the investigations are still basic more than applied. One problem with which
researchers are beginning to come to grips, though, is determining the kinds if molecules
needed to make the transistors and other electronic components that will go into the
molecular electronic devices, some of the molecules are like bacteriorhodopsin in that
their two states flip back and forth when exposed to wavelengths of light. These
molecules would be the equivalent of an optical switch on which on state is on and the
other state is off. Optical switches have been difficult to make from standard
semiconductors. Bacteriorhodopsin is the light-harvested pigment of purple bacteria
living in salt marshes outside San Francisco. The compound consists of a pigment core
surrounded by a protein that stabilizes the pigment. Birge has capitalized on the clear cut
distinction between the two states of bacteriorhodopsin to make readable-write able
optical memory devices. Laser disks, are read-only optical memory devices, once encoded
the data cannot be changed. Birge has been able to form a thin film of bacteriorhodopsin
on quartz plates that can then be used as optical memory disks. The film consists of a
thousand one-molecule thick layers deposited one layer at a time using the Langmuir-
Blodgett technique. A quartz plate is dipped into water whose surface is covered with
bacteriorhodopsin. When the plate is withdrawn at a certain speed, a monolayer of
rhodopsin adheres to the plate with all the molecules oriented in the same direction.
Repeating this process deposits a second layer, then a third, and so on. Information is
stored by assigning 0 to the green state and 1 to the orange state. Miniature lasers of the
type use thin fiber optic communications devices are used to switch between the two
states. Irradiating the disk with a green laser converts the green state to the orange state,
storing a 1, resetting the bit is accomplished by irradiating the same small area of the dusk
with a red laser. Data stored on the disk are read by using both lasers. The disk would be
scanned with the red laser and any bit with a value 1 would be reset using the green laser.
This is analogous to the way in which both magnetic and electrical memories are read
today, but with one important difference: "Because the two states take only five
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PROTEIN MEMORY
picoseconds (five trillionths of a second) to flip back and forth, information storage and
retrieval are much faster than anything you could ever do magnetically or electrically,"
explained Birge. In theory, each pigment molecule could store one bit of information. In
practice, however approximately 100,000 molecules are sued. The laser beam as a
diameter if approximately 10 molecules and penetrates through the 1,000 molecule thick
layer. Although this reduces the amount of information that can be stored on each disk, it
does provide fidelity though redundancy. "We can have half the molecules or more in a
disk fall apart and there would still be enough excited by the laser at each spot to provide
accurate data storage," said Birge. And even using 100,000 molecules per data bit, an old
5.25 inch floppy disk could store well over 500 megabytes of data. Faster, higher-density
disk storage is a laudable goal, but the big stakes are in improving on semiconductor
components. Birge, for example, is developing a random access chip using the
bacteriorhodopsin system. Instead of having millions of transistors wired together on a
slab of silicon, there would be millions of tiny lasers pointed at a film of
bacteriorhodopsin. "These RAM chips would actually be a little bigger than what we
have," he said, "but they would still be 1,000 times faster because the molecular
components work so much faster than ones made of semiconductor materials."
Why Bacteriorhodopsin?
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deposits attests to the extreme durability and stability of these structures. In viable
organisms BR functions in high efficiency at temperatures as high as 140˚C, in near-
saturating concentrations of salt, and in highly acidic environments. Specific lipids of the
purple membrane are required for normal bacteriorhodopsin structure, function, and photo
cycle kinetics. At ambient temperatures, the membranes are in a liquid crystalline state
that provides optimal functioning of the BR. Adaptations of the membrane lipids allow
maintenance of the liquid crystalline state even as the indigenous conditions change.
Nevertheless, as a consequence of light absorption, BR initiates a photo cycle through
structurally distinctive conformations, causing tractable optical and electronic properties
of the protein. The characteristics of the lipids in the membrane dictate the large-
amplitude motions of BR, and by consequence the broad utility of BR in bioelectronic
devices. The research to be developed under this topic would have military and civilian
importance. Some of the bionanotechnological applications that are anticipated include:
ultra rapid optical data acquisition with parallel processing capabilities and extreme high
density holographic three-dimensional data and image storage. Adapting natural
membranes or engineering alterations in those structures would have significant
advantages over the artificial membranes that are currently employed. The naturally
derived membranes would be biodegradable, eliminating the necessity for the disposal of
products that would be toxic or recalcitrant to decomposition. Another major advantage
would be the broad utility of the membranes with a variety of bioengineered
bacteriorhodopsin molecules. Using site directed mutagenesis it is known that the
molecular and physical properties of the protein molecule can be altered. Thus, with the
molecular biological tailoring of bacteriorhodopsin for specific phototropic properties, it
will be possible to optimize the photo cyclic intermediates for distinctive properties in
particular applications utilizing natural membranes.
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4.10,000 molecules/bit
Using the purple membrane from the bacterium Halobacterium Halobium, Prof.
Robert Birge and his group at Syracuse University have made a working optical bistable
switch, fabricated in a monolayer by self-assembly, that reliably stores data with 10,000
molecules per bit. The molecule switches in 500 femtoseconds--that's 1/2000 of a
nanosecond, and the actual speed of the memory is currently limited by how fast you can
steer a laser beam to the correct spot on the memory.
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PROTEIN MEMORY
Retinal separates a cytoplasmic from an extra cellular half channel that is lined
by amino acids crucial for efficient proton transport by BR (especially Asp-96 in the
cytoplasmic and Asp-85 in the extra cellular half channel). The Schiff base between
retinal and Lys-216 is located at the center of this channel. To allow vectorial proton
transport, de- and reprotonation of the Schiff base must occur from different sides of
the membrane. Thus, the accessibility of the Schiff base for Asp-96 and Asp-85 must be
switched during the catalytic cycle. The geometry of the retinal, the protonation state of
the Schiff base, and its precise electrostatic interaction with the surrounding charges
(Asp-85, Asp-212, Arg-82) and dipoles tune the absorption maximum to fit its
biological function.
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biophysical techniques, the exact nature of the changes in each step of the cycle has
been determined and has been related to transport function.
The cycle can be formally described in terms of six steps of isomerization (I),
ion transport (T), and accessibility change (switch S). Retinal first photo-isomerizes
from all-trans to a 13-cis configuration followed by a proton transfer from the Schiff
base to the proton acceptor Asp-85. To allow vectoriality, reprotonation of the Schiff
base from Asp-85 must be excluded. Thus, its accessibility is switched from extra
cellular to intracellular. The Schiff base is then reprotonated from Asp-96 in the
cytoplasmic channel. After reprotonation of Asp-96 from the cytoplasmic surface,
retinal reisomerizes thermally and the accessibility of the Schiff base switches back to
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extra cellular to reestablish the initial state. These steps represent the minimal number
of steps needed to account for vectorial catalysis in wild-type bacteriorhodopsin.
The K590 intermediate is transformed to the L550 intermediate within 2 µs. The
hydrogen bonding interaction in the extra cellular channel between the protonated
Schiff base and Asp-85, which involves a water molecule, is strengthened.
The M state is reached from the L state within several microseconds. This
transition involves transfer of a proton from the Schiff base to Asp-85 in the extra
cellular half-channel.
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PROTEIN MEMORY
To allow vectorial proton transport, de- and reprotonation of the Schiff base
must occur from different sides of the membrane. This accessibility switch occurs at the
level of the M intermediate: M410 (EC) to M410 (CP). Thus, the originally described
"M" intermediate is in fact split into two or more different intermediates all having
yellow color.
The transition of the N560 to the O640 intermediate is the thermal 13-cis to all-
trans isomerization of retinal in the environment of protonated Asp-96 and protonated
Asp-85.
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An important tool for these studies, and also for spectroscopic investigations on
structure and dynamics, is the possibility to produce specifically modified proteins by
site directed mutagenesis and homologous over expression. By this method the role of
individual amino acid residues for the transport mechanism can be investigated, or
reporter molecules can be introduced at certain positions. Several mutants interfere with
the photo cycle and proton transport and may permit to trap intermediates of the cycle.
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PROTEIN MEMORY
Bacteriorhodopsin, after being initially exposed to light (in our case a laser beam),
will change to between photo isomers during the main photochemical event when it
absorbs energy from a second laser beam. This process is known as sequential one-photon
architecture, or two-photon absorption. While early efforts to make use of this property
were carried out at cryogenic temperatures (liquid nitrogen temperatures), modern
research has made use of the different states of bacteriorhodopsin to carry out these
operations at room-temperature.
Upon initially being struck with light (a laser beam), the bacteriorhodopsin alters
its structure from the bR native state to a form we will call the O state. After a second
pulse of light, the O state then changes to a P form, which quickly reverts to a very stable
Q state, which is stable for long periods of time (even up to several years).
The data writing technique proposed by Dr. Birge involves the use of a three-
dimensional data storage system. In this case, a cube of bacteriorhodopsin in a polymer
gel is surrounded by two arrays of laser beams placed at 90 degree angles from each
other. One array of lasers, all set to green (called "paging" beams), activates the photo
cycle of the protein in any selected square plane, or page, within the cube. After a few
milliseconds, the number of intermediate O stages of bacteriorhodopsin reaches near
maximum. Now the other set, or array, of lasers - this time of red beams - is fired.
The second array is programmed to strike only the region of the activated square
where the data bits are to be written, switching molecules there to the P structure. The P
intermediate then quickly relaxes to the highly stable Q state. We then assign the initially-
excited state, the O state, to a binary value of 0, and the P and Q states are assigned a
binary value of 1. This process is now analogous to the binary switching system which is
used in existing semiconductor and magnetic memories. However, because the laser array
can activate molecules in various places throughout the selected page or plane, multiple
data locations (known as "addresses") can be written simultaneously - or in other words,
in parallel.
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PROTEIN MEMORY
The system for reading stored memory, either during processing or extraction of a
result relies on the selective absorption of red light by the O intermediate state of
bacteriorhodopsin. To read multiple bits of data in parallel, we start just as we do in the
writing process. First, the green paging beam is fired at the square of protein to be read.
After two milliseconds (enough time for the maximum amount of O intermediates to
appear), the entire red laser array is turned on at a very low intensity of red light. The
molecules that are in the binary state 1 (P or Q intermediate states) do not absorb the red
light, or change their states, as they have already been excited by the intense red light
during the data writing stage.
However, the molecules which started out in the binary state 0 (the O intermediate
state), do absorb the low-intensity red beams. A detector then images (reads) the light
passing through the cube of memory and records the location of the O and P or Q
structures; or in terms of binary code, the detector reads 0's and 1's. The process is
complete in approximately 10 milliseconds, a rate of 10 megabytes per second for each
page of memory.
Clearly, there are many advantages to protein-based memory, among the most
significant being cost, size, and memory density. However, there are still several barriers
standing in the way of mass-produced protein-based memories.
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PROTEIN MEMORY
Data Erasing
To erase data; a brief pulse from a blue laser returns molecules in the Q state back
to the rest state. The blue light doesn't necessarily have to be a laser; you can bulk-erase
the cuvette by exposing it to an incandescent light with ultraviolet output.
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PROTEIN MEMORY
In Protein memory the read/write operations use two additional parity bits to guard against
errors. A page of data can be read nondestructively about 5000 times.Each page is
monitored by a counter and after 1024 reads, the page is refreshed by a new write operation.
Merits
• .The system has the ability to operate over a wider range of temperatures than the
semiconductor memory.
• The data is stable, ie the memory system’s power is turned off, the molecules retain
their information.
• This is portable, ie we can remove small data cubes and ship GBs of data around for
storage or backups.
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Conclusion
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